Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.

Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

Case Report: Post-gastrectomy reactive hyperinsulinemic hypoglicaemia: glucose trends before and after canagliflozin treatment.

The pathogenesis of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia is not yet fully clarified. Recent studies suggest an up-regulation of the intestinal glucose transporter SGLT-1 aimed to prevent carbohydrate malabsorption. The overexpression of SGLT-1 could therefore represents one of the mechanisms underlying the wide glycemic excursions found in patients after gastrectomy, but studies investigating the use of SGLT-1/SGLT-2 inhibitors in patients with post-gastrectomy reactive hyperinsulinemic hypoglycaemia are very scant in the literature. We report the case of a 37-year-old non diabetic man who frequently presented symptoms of hypoglycaemia in the postprandial period. In 2012, he underwent Roux en-Y gastric bypass (RYGB) and after two years, he started to experience typical symptoms of reactive hyperinsulinaemic hypoglycaemia. We suggested healthy modifications of dietary habits and periodic follow-up visits with a dietitian. After three months, the patient still presented symptoms of reactive hypoglycaemia; we provided him with Flash Glucose Monitoring (FGM) to assess trend of glucose levels in interstitial fluid during the day and we decided to introduce canagliflozin 300 mg/day before the main meal. Hypoglycaemic events previously referred by the patient and clearly recorded by FGM completely disappeared taking canagliflozin. We found a reduction of time spent in hypoglycaemia, an improvement of glycemic variability and an increase of time in target range. It was also noted a reduction of time spent in hyperglicemia with consequent improvement of average glucose values and of glucose main indicator. This is the first report with FGM supporting a role of canagliflozin in the management of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia. Our preliminary results are very limited but in line with those of the literature and showed for the first time a reduction of hypoglycaemic events and an improvement of glycemic variability through a flash glucose monitoring system. Further studies are mandatory to confirm this therapeutic opportunity.

[Fine specificity of anti-ß2glycoprotein I antibodies in systemic autoimmune diseases is mostly directed against domain 1]. / La fine specificità degli anticorpi anti-ß2 glicoproteina I nelle malattie autoimmune sistemiche è prevalentemente diretta verso il dominio 1.

OBJECTIVE: Anti-ß2 GPI are a formal laboratory criterion for the antiphospholipid syndrome (APS). They were demonstrated to be a risk factor for thrombosis and fetal losses but can also be detected in patients with systemic autoimmune disease (SAD), in healthy adults individuals and pre-school children. It has been suggested that different subpopulations of anti-ß2GPI may carry different pathogenetic potential: autoantibodies against Domain1 seem to be associated with thrombosis; autoantibodies against Domain4/5 have been identified in patients with non-thrombotic conditions. METHODS: We studied 48 patients with SAD (32 systemic lupus erythematosus, 16 undifferentiated connettive tissue disease), 64 patients with APS, 57 one-year-old healthy children born to mother with SAD, 33 children with atopic dermatitis. All subjects were IgG anti-ß2 GPI positive. The specificity of anti-ß2 GPI was investigated using ELISA research products containing recombinant ß2 GPI D1 and D4/5 antigens. Cut-off values are calculated as 95th percentile on 100 NHD. IgG anti-ß2 GPI were tested at a validated home-made ELISA routinely performed in our laboratory. No thrombotic events were recordered in patients with SAD and in both groups of children. RESULTS: Patients with SAD and APS showed prevalent reactivity for D1 while children in both groups preferentially recognize D4/5. CONCLUSIONS: IgG anti-ß2 GPI against D1 seem to cluster in patients with systemic autoimmune conditions. Their pathogenic potential in determine APS manifestations may be mitigated by adequate prophylaxis.

[Subpopulations of anti-ß2glycoprotein I antibodies with different pathogenic potential: fine specificity against the domains of ß2glycoprotein I]. / Sottopopolazioni di anticorpi anti-ß2glicoproteina I con diverso potenziale patogenetico: fine specificità nei confronti dei domini della ß2glicoproteina I.

OBJECTIVE: Anti-ß2glycoprotein I antibodies (a-ß2GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-ß2GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a-ß2GPI in different clinical situations. METHODS: We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-ß2GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-ß2GPI positive. IgG a-ß2GPI were performed by homemade ELISA, while IgG a-ß2GPI D1 and D4/5 were tested on research ELISAs containing recombinant ß2GPI domains antigens. RESULTS: One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-ß2GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-ß2GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children. CONCLUSIONS: A-ß2GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the "innocent" profile of a-ß2GPI in children.

Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study.

OBJECTIVES: To asses risk factors for a first thrombotic event in antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of prophylactic treatments. METHODS: Recruitment criteria were age 18-65 years, no history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM anticardiolipin antibody (aCL) on > or =2 occasions at least 6 weeks apart. Demographic, laboratory and clinical parameters were collected at enrolment and at the time of the thrombotic event. RESULTS: 370 patients/subjects (mean (SD) age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of 59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event during follow-up. Hypertension and medium/high levels of IgG aCL were identified by multivariate logistic regression analysis as independent risk factors for thrombosis. Thromboprophylaxis during high-risk and long-term periods was significantly protective. CONCLUSIONS: Hypertension or medium/high titres of IgG aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers and primary prophylaxis is protective.

Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers.

BACKGROUND: Recommendations for the treatment of aPL-positive patients with pregnancy morbidity are based on a limited number of well-designed clinical trials. However, the management of pregnant aPL-positive women still displays several open questions. OBJECTIVE: To determine the practice patterns of experienced physicians in the management of the controversial aspects of aPL pregnancies. METHODS: A questionnaire reproducing debated conditions was initially sent to the Advisory Board members (ABMs) of the 12th Congress of aPL and the Fifth Conference on Sex Hormones, Pregnancy and Rheumatic Diseases (Florence, Italy, April 2007), and then the same questionnaire was posted at the Hospital for Special Surgery (www.hss.edu) website and all attendees (ATS) of the above meetings were invited to participate via e-mail. Answers have been collected and analysed in a descriptive fashion and responses of the two groups evaluated by Chi-square or Fisher's exact test. RESULTS: As a whole 75 responses from the ABMs and ATS were included in the analysis. In general, there was no significant difference between the opinions of two groups. CONCLUSIONS: Management recommendations displayed reasonable consistence: (i) for the use of low-dose aspirin and low-molecular weight heparin during pregnancy and during ovarian stimulation for in vitro fertilization; (ii) against oestrogen-containing oral contraceptives; and (iii) for the use of anticoagulants in the post-partum period.

[Anti-TNFalpha agents in elderly patients with rheumatoid arthritis: a study of a group of 105 over sixty five years old patients]. / I farmaci biologici anti-TNFalpha nel paziente anziano affetto da artrite reumatoide: studio di una coorte di 105 pazienti ultra-sessantacinquenni.

OBJECTIVE: To evaluate the efficacy and the safety of anti-TNF alfa treatment in elderly patients (>/=65 years old) with active rheumatoid arthritis (RA), in comparison with younger (17-65 years old). METHODS: We considered retrospectively 295 patients, affected by RA and treated with anti-TNF alfa drugs. They were divided in two groups, according to their age, and followed up for two years: over-65-years old patients (190) and under-65-years old patients (105). Effectiveness of drugs was assessed analyzing RA disease activity (DAS28, DAS44, SDAI), functional status (HAQ) and serological parameters (CRP) before and after anti-TNF alfa therapy. Safety was studied considering discontinuation rate of biological disease-modifying antirheumatic drugs, and collateral events rate. RESULTS: At baseline, elderly patients showed higher disease activity's score (DAS 28, DAS44, SDAI, HAQ) with important loss of articular function (worse quality of life, HAQ) than younger patients (p<0.05). During the therapy, improvement in clinical parameters was observed (DAS28, DAS44 and SDAI) with no significant difference between the two groups. In elderly patients disability index, on the contrary, improved less than in younger (p<0.05). After treatment, also CRP decreased less in elderly patients (p<0.05). During the follow-up, 74 over-65-years old patients (38.95%) and 116 under-65-years old patients (38.05%) discontinued anti-TNF alfa therapy because of loss of efficacy (20.52% vs 11.42%), severe adverse events (17.34% vs 25.67%), voluntary discontinuation or good clinical response (1% vs 0.95%). No differences were shown about the frequency and reasons of anti-TNF alfa withdrawal (p>0.05). CONCLUSIONS: Anti-TNF alfa treatment was efficacious and safe in both groups of patients. These drugs induced improvement in disease activity, apart from the age. No functional improvement was observed in HAQ, showing the irreversible loss of articular function and the incomplete recovery in elderly patients. Age doesn't interfere with the possibility to treat elderly patients with anti-TNF alfa drugs.

Morphology development during single droplet drying of mixed component formulations and milk.

We report on the influence of selected components and their mixtures on the development of the morphology during drying of single droplets and extend the results to the morphology of whole milk powder particles. Sessile single droplet drying and acoustic levitation methods were employed to study single droplet drying. The influence of carbohydrates (lactose and maltodextrin DE12) and proteins (micellar casein or whey protein) on morphology development is very different, since upon concentration protein systems will jam and undergo a colloidal glass transition, whereas carbohydrate systems will gradually increase in viscosity as a consequence of the concentration. Whey protein gives relatively rigid shells due to jamming of the "hard sphere" proteins, while casein micelles behave as "soft spheres" that can deform after jamming, which gives flexibility to the shell during drying. The influence of the carbohydrates on the final morphology was found much larger than the influence of the proteins. Caseins influenced morphology only in mixtures with lactose at higher concentrations due to its high voluminosity. Similar observations were done for whole milk, where fat appeared to have no influence. With maltodextrin the influence of the casein was again observed in the shape and smoothness of wrinkles. Both sessile and levitated droplet drying methods provide a similar and consistent view on morphology development.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

DNA-based selection and screening of peptide ligands.

Phage display selection strategies rely on the physical link between the displayed heterologous protein ligand and the DNA encoding it. Thus, genes expressing a ligand with a specific binding affinity can be selected rapidly. To improve the specificity and sensitivity of this technology for potential use in identifying ligands to a specific antibody present in a complex mixture, we incorporated a DNA selection step along with the phage display technology. Ligands for hepatitis C virus (HCV) antibodies present in serum were identified by panning a phage-displayed random peptide library against pools of serum HCV antibodies. An additional DNA hybridization screening step using single-stranded DNA isolated from one of the pools increased the specificity and sensitivity, resulting in the selection of an HCV antibody ligand with diagnostic potential.

Influence of buttermilk powder or buttermilk addition on phospholipid content, chemical and bio-chemical composition and bacterial viability in Cheddar style-cheese.

The effect of buttermilk powder addition post-curd formation or buttermilk addition to cheese milk on total and individual phospholipid content, chemical composition, enzyme activity, microbial populations and microstructure within Cheddar-style cheese was investigated. Buttermilk or buttermilk powder addition resulted in significant increases in total phospholipid content and their distribution throughout the cheese matrix. Addition of 10% buttermilk powder resulted in higher phospholipid content, moisture, pH and salt in moisture levels, and lower fat, fat in dry matter, L. helveticus and non-starter bacteria levels in cheeses. Buttermilk powder inclusion resulted in lower pH4.6/Soluble Nitrogen (SN) levels and significantly lower free amino acid levels in 10% buttermilk powder cheeses. Buttermilk addition provided a more porous cheese microstructure with greater fat globule coalescence and increased free fat pools, while also increasing moisture and decreasing protein, fat and pH levels. Addition of buttermilk in liquid or powdered form offers potential for new cheeses with associated health benefits.

Recognition by human sera and immunogenicity of HBsAg mimotopes selected from an M13 phage display library.

We used two mouse monoclonal antibodies (mAb) specific for the human hepatitis B virus surface antigen (HBsAg) to screen a random peptide library of 15 amino-acid residues displayed as a fusion to protein III of filamentous phage M13. By a combination of affinity selection, immuno-screening and ELISA techniques, we selected peptides that are recognized by the anti-HBsAg mAb and show aa similarity with the natural antigen. The selected phage-displayed epitopes (phagotopes) behave as antigenic mimics of HBsAg. One phagotope is specifically recognized by human sera from HBsAg-immunized individuals, pointing to the possible use of phagotopes as markers to detect the presence of specific Ab in the serum. The same phagotope also elicits Ab directed against HBsAg in mice, indicating that mAb-selected phagotopes can also be immunogenic mimics of the natural antigen. These findings demonstrate that it is possible to identify disease-specific epitopes that can be used as diagnostic reagents and as leads for the development of acellular vaccines.

"Affinity maturation" of ligands for HCV-specific serum antibodies.

We have previously screened a phage-displayed random peptide library using sera from patients and identified ligands binding to antibodies specifically associated with the hepatitis C virus infection. The ability of these peptides to detect HCV-specific antibodies was improved through an in vitro procedure which mimics the natural process of antibody affinity maturation operating in secondary immune response. Libraries were generated by mutating the sequence of the original peptide through a protocol that efficiently introduced substitution, insertion and deletion mutations on a single or population of clones. Screening these libraries isolated mutants that displayed increased specific reactivity with a broader range of sera from HCV-infected patients. Several variants of the original peptide were identified which discriminate between the various components of the specific polyclonal response. This methodology to select artificial ligands from RPL using sera and to enhance their diagnostic properties by affinity maturation makes the development of a diagnostic assay to detect disease-associated antibodies feasible, without requiring the natural antigen.

Individual knowledge of emotions in asthmatic children.

Twenty male asthmatic children (ages 9-11) and their controls were interviewed regarding their concept of emotion using the interview format developed by Harris et al. (1981). The purpose of the study was to examine the asthmatic children's views on the nature and effects of happiness, anger and fear, together with strategies of self-control. The results indicate that healthy and asthmatic children have a different individual view of emotion. The most relevant finding concerns the different way in which healthy and asthmatic children consider fear: the most frequent view of fear in healthy children is similar to a behaviouristic model of emotion, while asthmatic children express a notion very similar to a cognitive model. Regarding anger, almost all healthy children believe themselves capable of exerting self-control whether on the inner mental components or on its outer expression, where a change of direction of mental processes is the only way asthmatic children see to modify their anger. The implications of these findings both for a description of asthmatic personality and therapy are outlined.

Detection of sentinel nodes by lymphoscintigraphy and gamma probe guided surgery in vulvar neoplasia.

BACKGROUND: Pathologic lymph node status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Intraoperative lymphoscintigraphy associated with gamma detecting probe-guided surgery has proved to be reliable in the detection of sentinel node (SN) involvement in melanoma and breast cancer patients. The present study evaluates the feasibility of the surgical identification of inguinal sentinel nodes using lymphoscintigraphy and a gamma detecting probe in patients with early vulvar cancer. METHODS: Technetium-99-labeled colloid human albumin was administered perilesionally in 44 patients. Twenty patients had T1 and 23 had T2 invasive epidermoid vulvar cancer; one patient had a lower-third vaginal cancer. An intraoperative gamma detecting probe was used to identify SNs during surgery. Complete inguinofemoral node dissection was subsequently performed. SNs underwent separate pathologic evaluation. RESULTS: A total of 77 groins were dissected in 44 patients. SNs were identified in all the studied groins. Thirteen cases had positive nodes: the SN was positive in all of them; in 10 cases the SN was the only positive node. Thirty-one patients showed negative SNs: all of them were negative for lymph node metastasis. CONCLUSIONS: Lymphoscintigraphy and SN biopsy under gamma detecting probe guidance proved to be an easy and reliable method for detection of SNs in early vulvar cancer. If these preliminary data will be confirmed, the technique would represent a real progress towards less aggressive treatment in patients with vulvar cancer.

Combined Pap smear, cervicography and HPV DNA testing in the detection of cervical intraepithelial neoplasia and cancer.

OBJECTIVE: The sensitivity of the Pap smear (PAP) continues to be the subject of debate. During the past several years, cervicography (CER) and HPV DNA testing have been suggested as optional tools in the screening of cervical cancer precursors. STUDY DESIGN: The performance characteristics of PAP, CER and HPV DNA testing (hybrid capture test [HCT]) in all potential combinations were evaluated in a series of 1,030 women (aged 16-70, median, 33), subjected to colposcopy (COLPO) as the reference tool. RESULTS: Of the 992 evaluable cases, 402/992 (41%) had positive COLPO (i.e., an abnormal transformation zone). Of them, 298 women underwent directed punch biopsy, while of the COLPO negative patients, 18/93 positive by at least one of the three tests had endocervical curettage. Of the 402 COLPO positive women, 146 (36%) remained negative on all tests, whereas 256 (64%) had at least one positive test. There were 84 cervical intraepithelial neoplasia (CIN) 2 and 3 lesions and 6 invasive carcinomas. Of the former, 10 were detected by PAP alone, 4 by CER alone and 3 by HCT alone. Three of the 6 carcinomas were HCT negative. The predictive value (PPV) of a positive test was 45% for PAP, 51% for CER and 48% for HCT. The combinations of PAP with CER (for PAP negative cases) and PAP with HCT were more sensitive for CIN 2 and 3 (95% and 94%, respectively) as compared with PAP alone but were associated with a significant decrease in specificity (44% and 46% vs. 57%, respectively). However, both combinations retained a PPV (43%) similar to that of PAP alone (45%). CONCLUSION: The potential combinations of PAP with CER and with HCT were more sensitive in detecting CIN 2 and 3 as compared with PAP alone and retained a PPV similar to that of PAP.

Assessment of risk factors and human papillomavirus (HPV) related pathogenetic mechanisms of CIN in HIV-positive and HIV-negative women. Study design and baseline data of the HPV-PathogenISS study.

OBJECTIVES: In women with HIV-associated immunosuppression, HPV infections have an increased risk of progression to high-grade cervical intraepithelial neoplasia (CIN). With the HAART-induced prolonged survival and more protracted clinical course of AIDS, progression of CIN to cervical cancer (CC) has become a clinically relevant issue, and the mechanisms responsible for HIV-HPV interactions need further elucidation. The study design and analysis of the baseline data of our new project are presented. MATERIAL AND METHODS: This project is a combination of a prospective cohort study of HIV- and HIV+ women, and a retrospective analysis of CIN lesions and cervical cancer. Up to the present, 244 women have been enrolled (17 HIV+) and subjected to epidemiological interview, colposcopic examination, sampling for HPV testing and typing (PCR, InnoLiPA), and HPV serology. The retrospective series of biopsies were analysed for 13 biomarkers (monitoring key molecular events) using immunohistochemistry and tested for HPV by PCR and TaqMan. RESULTS: HIV- and HIV+ women differ in their exposure status to many of the key epidemiological risk factors of cervical cancer, the most significant ones being number of sexual partners (p = 0.0001), age at onset of sexual activity (p = 0.002), and contraception (yes-no) (p = 0.009). The differences in the baseline clinical observations are less dramatic; HIV-positive women had more frequent HSIL PAP tests (p = 0.040), CIN2 or higher in cervical biopsy (p = 0.049), and external genital warts (p = 0.019). The factors predicting intermediate endpoint markers of cervical cancer, i.e., HSIL PAP smear, ATZ2 in colposcopy, and high-grade CIN in biopsy were analysed in univariate and multivariate regression models. All factors significant in univariate analysis were entered in the multivariate model; HIV-status and Pap smear history maintained their independent predictive power of the HSIL Pap test. The most powerful predictor of ATZ2 colposcopy was HSIL in Pap test. Only the HSIL Pap test and ATZ2 colposcopy remained significant independent predictors of high-grade CIN (p = 0.0001 and p = 0.008, respectively) in the multivariate model. CONCLUSIONS: The three intermediate endpoint markers are closely interrelated, but predicted in part by different covariantes in the causal pathway to cervical cancer. To elucidate whether the increased risk of HIV-positive women to high-grade CIN is due a) to their different exposure status to the risk factors, b) to the direct effects of HIV, or c) to molecular interactions between HIV and HPV, we need to complete these analyses separately in HIV+ and HIV- women.

Neuroglobin, a pro-survival player in estrogen receptor α-positive cancer cells.

Recently, we reported that human neuroglobin (NGB) is a new player in the signal transduction pathways that lead to 17ß-estradiol (E2)-induced neuron survival. Indeed, E2 induces in neuron mitochondria the enhancement of NGB level, which in turn impairs the activation of a pro-apoptotic cascade. Nowadays, the existence of a similar pathway activated by E2 in non-neuronal cells is completely unknown. Here, the role of E2-induced NGB upregulation in tumor cells is reported. E2 induced the upregulation of NGB in a dose- and time-dependent manner in MCF-7, HepG2, SK-N-BE, and HeLa cells transfected with estrogen receptor α (ERα), whereas E2 was unable to modulate the NGB expression in the ERα-devoid HeLa cells. Both transcriptional and extranuclear ERα signals were required for the E2-dependent upregulation of NGB in MCF-7 and HepG2 cell lines. E2 stimulation modified NGB intracellular localization, inducing a significant reduction of NGB in the nucleus with a parallel increase of NGB in the mitochondria in both HepG2 and MCF-7 cells. Remarkably, E2 pretreatment did not counteract the H2O2-induced caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage, as well as Bcl-2 overexpression in MCF-7 and HepG2 cells in which NGB was stably silenced by using shRNA lentiviral particles, highlighting the pivotal role of NGB in E2-induced antiapoptotic pathways in cancer cells. Present results indicate that the E2-induced NGB upregulation in cancer cells could represent a defense mechanism of E2-related cancers rendering them insensitive to oxidative stress. As a whole, these data open new avenues to develop therapeutic strategies against E2-related cancers.